Respiratory transmission of adenovirus types 4 and 7 is associated with the development of respiratory illness. However, enteric administration of the viruses produces a silent infection localized to the intestinal tract which is capable of preventing subsequent respiratory illness caused by these viruses. This observation served as the basis for the development in LID of the live enteric adenovirus type 4 and 7 vaccines. An extensive experience in the use of these vaccines has been gained over the last 20 years since the vaccine is administered routinely to all new recruits in the military. The safety and efficacy of these adenovirus vaccines make them ideal candidates for use as vectors for insertion and expression of foreign genes. Replication of recombinant adenovirus in the intestine should induce an immune response directed at the proteins of the foreign genes and hence confer resistance against the agents from which the genes were derived. The likelihood of the success of this general approach has already been shown by research scientists at Wyeth who were able to express hepatist B surface antigen by inserting and expressing the corresponding hepatitis B virus gene in the E1 and later in the E3 region of adenovirus type 5. It should be possible to construct adenovirus recombinants that allows packaging of foreign DNA (perhaps up to 5000 bases) after the deletion of non-essential adenovirus regions. We are testing this approach to develop recombinant rotavirus vaccines. The vaccine strains of adenovirus types 4 and 7 vaccines would seem to be safe vectors for foreign genes. Furthermore, infection in the intestines may result in local IgA responses which are particularly important for virus, such as the retroviruses, which produce mucosal infection.